SLAMF7 is a key molecule that promotes M1 polarization in lung tissue macrophages of high-fat diet-fed asthma mice model.

Objective: Investigating the regulatory role of Signaling lymphocyte activation molecule family 7 (SLAMF7) in the pathogenesis of asthma in a high fat-fed (HFD) mouse model, providing targets for treating obese asthma.

Methods: We constructed a mouse model of obese asthma, and Quantitative real-time RT-PCR (qPCR) for the detection of mRNA levels of SLAMF7 and M1 polarization markers of macrophages. Lung tissue levels of SLAMF7 protein, macrophage M1 polarization markers, and neutrophil markers were measured by Western blotting. The proportions of SLAMF7 macrophages and neutrophils in bronchoalveolar lavage fluid (BALF) were determined by flow cytometry. Neutrophil inflammatory cytokine levels were determined by Enzyme-linked immunosorbent assay (ELISA). Immunofluorescence performed the colocalization of SLAMF7 and inducible nitric oxide synthase (iNOS). The regulation of SLAMF7 on M1 polarization of macrophages was verified by cell experiments.

Results: The group of HFD asthmatic mice had more severe airway inflammation and mucus secretion. They also had higher SLAMF7 levels, airway neutrophil inflammation and M1 polarization of macrophages in lung tissue. SLAMF7 overexpression increased M1 polarization, and SLAMF7 knockdown decreased M1 polarization. The expression change of SLAMF7 affects the expression of NR4A1 and RUNX3, inhibiting NR4A1 and promoting RUNX3.

Conclusion: SLAMF7 expression is increased in obese asthma mice, accompanied by neutrophil infiltration and enhanced M1 polarization. SLAMF7 promotes M1 polarization may be through the NR4A1-RUNX3 axis, suppressing NR4A1, and promoting RUNX3.